High-strength materials such as metals or ceramics are widely used in medical fields as prosthesis covering fractured sections, such as bone prosthesis or dental prosthesis (artificial dental roots) or as prosthesis for a physical activity, such as joint prostheses. Recent developments have seen the active application of metals to artificial circulatory system. Consequently, there is a need for materials with mechanical strength as well as biocompatibility. Here the term “biocompatibility” means the property of preventing blood coagulation reactions or suitable adaptability of the inserted section to soft tissue. This sort of biocompatibility is indispensable for in vivo medical devices.
A technique is known of applying 2-methacryloyloxyethyl phosphorylcholine (hereinafter referred to as “MPC”) which has superior biocompatibility as a medical polymer material. Conventionally, many biocompatible MPC polymers have been used in the form of an MPC copolymer containing hydrophobic groups resulting from the copolymerization of MPC with monomers containing hydrophobic groups. However in case that the resulting copolymer is coated onto the surface of the substrate (“surface substrate”) to be used in a medical device, few problems have, if in a short timeframe, arisen by being contacted with blood. However it is quite likely for the coating to remove from the surface substrate during long-term use.
In order to avoid these problems, a technique has been disclosed in which a coating material containing a copolymer of a reactive co-monomer, such as a styrene monomer containing amino groups or methylacrylate containing amino groups, as well as a monomer containing phosphorylcholine analogous groups has been used to fix this copolymer covalently to the substrate surface (Patent Document 1). However this technique has not generally been commercially applied due to the high price of styrene monomers containing amino groups or methylacrylate containing amino groups.
Another method has been disclosed in which chemical bonding is used to fix an MPC copolymer containing amino groups as well as an MPC copolymer containing epoxy groups to the surface substrate in a medical device (Patent Document 2 and Patent Document 3). However difficulties have been encountered in fixing the MPC copolymer containing amino groups to the substrate surface depending on the ratio of amino group content. As a result, the coating may become fragile.
A method has been disclosed in which a random copolymer comprising allylamine and phosphorylcholine analogue groups is fixed to a medical device (Patent Document 4). For example, in case that a coated medical device is made of a metallic material, a polymer 4-methacryloxyethyltrimellitate anhydride (hereinafter referred to as “4-META”) is used as a binder. The acid anhydride group contained in the 4-META polymer has superior reactivity with respect to an amino group in the random copolymer formed from allylamine and phosphorylcholine analogous groups. Consequently this binder enables a random copolymer to be fixed to the medical biomaterial.
However as described above, as the ratio of phosphorylcholine groups used in the copolymer decreases, problems have arisen that are associated with a deterioration in biocompatibility, hydrophily and surface lubricity.
Furthermore a suitable solution to coating loss resulting from long-term use has yet to be found. It has been reported that after 91 days of use, only 5% of MPC copolymer remained in titanium-based artificial heart system coated with MPC copolymer (Non-Patent Document 1).
Joint prostheses such as knee joint prostheses or hip joint prostheses have been used which are generally constructed by a combination of ultrahigh molecular weight polyethylene (hereinafter referred to as “UHMWPE”) and a cobalt-chromium (hereinafter referred to as “Co—Cr”) alloy. However in case that joint prostheses are used in vivo, UHMWPE wear debris produced by frictional motion entered between the acetabular cup and the living bone. The wear debris are engulfed by macrophages, osteolytic cytokines are released leading to possibility of inducing osteolysis. Osteolysis leads to the serious problem that the fixing strength between the joint prosthesis and the bone is weakened, thus resulting in a complication concerning joint arthroplasty, which is termed as loosening (Non-Patent Document 2).
Normally the linear wear of the UHMWPE ranges from 0.1 mm to 0.2 mm annually and therefore no problems arise immediately after joint arthroplasty. However after approximately five years, aseptic loosening occurs as described above. It is sometimes the case that the joint prostheses should be replaced, leading to a large burden on the patient.
A method of solving the problem of loosening is to reduce the amount of UHMWPE wear debris. Therefore various tests have been performed for the purpose of improving the combination of the material used on the joint surface or improving the material itself. Especially, UHMWPE cross-linked by means of an electron beam or a radioactive-ray (cross-linked polyethylene, hereinafter referred to as “CLPE”) has been actively researched in recent years.
Research is also being conducted to improve the bearing surface of UHMWPE or the like. The group led by Nobuyuki Yamamoto has produced a medical device having the biocompatibility and the surface lubricity, which is produced by fixing a random copolymer comprising allylamine and phosphorylcholine analogue groups to the surface of a medical device including a joint prosthesis (Patent Document 4). The group led by Kazuhiko Ishihara has produced a joint prosthesis in which polymer material is used which grafts polymerizable monomers containing a phosphorylcholine group onto a polymer joint prosthesis containing UHMWPE, thus suppressing the production of wear debris by reducing friction between the bearing surface of the joint prosthesis (Patent Document 5).
It has also been proposed to use a combination of hard-material members at the joint face instead of using polymer materials such as UHMWPE which can create abrasion. For example, a joint prosthesis is currently undergoing clinical uses, which is formed from a combination of a femoral head prosthesis made of a Co—Cr alloy and an acetabular cup prosthesis made of Co—Cr alloy (Non-Patent Document 3) or a combination of a femoral head prosthesis made of an alumina-ceramic and an acetabular cup prosthesis made of an alumina-ceramic (Non-Patent Document 4).
Patent Document 1: Japanese Unexamined Patent Publication (Kokai) No. 7-502053
Patent Document 2: Japanese Unexamined Patent Publication (Kokai) No. 7-184989
Patent Document 3: Japanese Unexamined Patent Publication (Kokai) No. 7-184990
Patent Document 4: International Publication No. WO 01/05855, pamphlet
Patent Document 5: Japanese Patent Unexamined Publication (Kokai) No. 2003-310649
Non-Patent Document 1: “In Vivo Evaluation of a MPC Polymer Coated Continuous Flow Left Ventricular Assist System” ARTIFICIAL ORGANS, VOL 27, No. 2, 2003
Non-Patent Document 2: “In vivo wear of polyethylene acetabular components” THE JOURNAL OF BONE AND JOINT SURGERY, VOL 75-B, No. 2, 1993
Non-Patent Document 3: “Engineering Issues and Wear Performance of Metal on Metal Hip Implants” CLINICAL ORTHOPAEDICS AND RELATED RESERCH, No. 333, 1996
Non-Patent Document 4: “Wear rates of ceramic-on-ceramic bearing surfaces in total hip implants: A 12-year follow-up study” THE JOURNAL OF ALTHROPLASTY, VOL 14, No. 7, 1999